Paediatrics: Inherited endocrine syndromes

Inherited endocrine syndromes

Multiple endocrine neoplasia

This is a family of endocrine neoplasia syndromes that are inherited in an autosomal dominant manner:

·  multiple endocrine neoplasia (MEN) type 1;

·  MEN type 2;

·  Von Hippel–Lindau (VHL) syndrome.

The molecular genetic defects for these syndromes have been identified and genetic screening is available. Patients with these conditions require close surveillance and screening (biochemistry, radiology, etc.).

Multiple endocrine neoplasia (MEN) type 1

The condition is characterized by the following clinical features.

·  Hyperparathyroidism (90%). Due to parathyroid hyperplasia. Usually presents in second decade of life.

·  Pancreatic endocrine tumours (75%). Typically multifocal, pancreatic islet cell tumours. Include insulinoma (60%); gastrinoma (30%); VIPoma (rare); glucagonoma (rare). Present in adulthood.

·  Pituitary adenomas (10–65%). Prolactinoma (60%); GH-secreting (30%).

·  Other features: thyroid adenoma; thymic/bronchial carcinoid tumours; lipomas.

Multiple endocrine neoplasia type 2

MEN type 2 belongs to a family of three syndromes (MEN type 2A; MEN type 2B; familial medullary thyroid cancer) characterized by activating mu-tations in the RET proto-oncogene. Medullary thyroid cancer is a common feature in all the syndromes.

MEN type 2A

·  Medullary thyroid cancer (90%).

·  Phaeochromocytoma (50%).

·  Parathyroid ademona (25%).

MEN type 2B

·  Medullary thyroid cancer (90%).

·  Phaeochromocytoma.

·  Mucosal/intestinal ganglioneuromas.

·  Marfanoid body habitus.

·  Hirschsprung’s disease.

Familial medullary thyroid cancer

Isolated medullary thyroid cancer.

von Hippel–Lindau syndrome (VHL)

This condition is due to a mutation in the VHL gene. This is a tumour re-pressor gene that is located on chromosome 3.

The condition is characterized by the following features:

·  Retinal haemangioblastomas (40%):

·  Uncommon before age 10yrs.

Bleeding and retinal detachment.

·CNS haemangioblastomas: 75% occur in cerebellum.

·Phaeochromocytomas (20%): bilateral in 40%.

·Renal cysts and carcinomas:

·  Late feature: from 4th decade.

·  Occur in 70% by age 60yrs.

·Pancreatic neuroendocrine tumours: uncommon. 50% malignant. Most are non-functioning tumours, but may be secreting (insulin, glucagons, VIP).

·Simple adenomas/cysts: uncommon.

·  Pancreas; liver; epididymis; lung.

·  Meningioma.

McCune–Albright Syndrome

Characterized by the following triad of clinical features:

·Skin: hyperpigmented (café au lait) macules.

·  classically, irregular edge (so-called ‘coast of Maine’ appearance);

·  do not cross midline.

·Polyostic fibrous dysplasia:

·  slowly progressive bone lesion;

·  any bones, although facial/base of skull bones most commonly affected.

·Autonomous endocrine gland hyperfunction:

·  ovary most commonly affected;

·  precocious puberty (gonadotrophin-indepdent);

·  thyroid (hyperthyroidism);

·  adrenal (Cushing’s syndrome);

·  pituitary (adenoma—gigantism);

·  parathyroid (hyperparathyroidism).

Neurofibromatosis

Two types of neurofibromatosis (NF) are recognized. Type 1 (NF-1; also known as von Recklinghausen’s disease) is an autosomal dominant condition due to a mutation of the NF-1 gene.

NF-1 may be associated with endocrine abnormalities:

·Hypothalamic/pituitary tumours: optic glioma (15%).

·GH deficiency.

·Precocious puberty.

Delayed puberty.